Active clinical trials for "Osteosarcoma"

Approximately 150 new cases of osteosarcoma are reported each year in France, of which 15 to 20% are metastatic. Further to the initial standard care, about 45% of the patients relapse within a median duration of 20 months. Result of the OS94 study results and of the investigation performed within the CRLCC, indicate that 25 to 30 patients (children and adults) experience an osteosarcoma relapse each year in FRANCE. According to several studies, the 5-year overall survival rate of patients in first relapse is 23-28%,with a median post relapse survival of 10 to 17 months. Multiple relapse cases are also reported in the COSS study, with a median time to second relapse of 0.8 year. At present, there is no reference treatment for the standard care of osteosarcoma relapse in FRANCE. Thiotepa is known for its antitumor effect in numerous malignant tumors. In 2007, a study from our institution reported that about 35% of all osteosarcoma relapses are treated with a high-dose thiotepa while the efficacy and tolerance of this therapeutic strategy have never been assessed. These results highlight the need to the evaluate the efficacy and tolerance of this high-dose of thiotepa within a clinical trial and its inclusion in the standard care of the osteosarcoma at relapse.

The goal of this clinical research study is to learn if treatment with the drug liposomal vincristine can shrink or slow the growth of the patient's cancer. The safety of this drug will also be studied.

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase I trial to study the effectiveness of liposomal doxorubicin in treating children who have refractory solid tumors.

RATIONALE: Inhaling aerosolized sargramostim before and after surgery may interfere with the growth of tumor cells and shrink the tumor so that it can be removed during surgery. Sargramostim may then kill any tumor cells remaining after surgery. This may be an effective treatment for osteosarcoma that has spread to the lung. PURPOSE: This phase II trial is studying how well inhaled sargramostim works in treating patients who are undergoing surgery for the first recurrence of osteosarcoma that has spread to the lung.

This protocol is designed to test the feasibility of the administration of vincristine, adriamycin and cytoxan, alternating with the newly developed regimen ifosfamide VP-16 as well as the efficacy of this therapy in addition to radiotherapy in producing complete responses and disease-free survival in patients with Ewing's sarcoma, primitive sarcoma of bone, peripheral neuroepithelioma, and soft tissue sarcoma. This will not be a randomized study but will be comparable to the large data base of similar patients treated on successive Pediatric Branch studies.

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Colony-stimulating factors such as G-CSF may increase the number of immune cells found in bone marrow or peripheral blood and may help a person's immune system recover from the side effects of chemotherapy. It is not yet known whether chemotherapy and surgery plus G-CSF is more effective than chemotherapy and surgery alone in treating patients with osteosarcoma. PURPOSE: Randomized phase III trial to compare the effectiveness combination chemotherapy and surgery with or without G-CSF in treating patients who have newly diagnosed osteosarcoma.

The suppression of IGF-I and growth hormone may significantly alter the pathobiology of osteosarcoma. SMS 201-955 pa LAR is a long acting analog of Somatostatin which inhibits the pituitary release of growth hormone, reducing levels of circulating IGF-I . Additional data on tamoxifen usage has also demonstrated a reduction in circulating IGF-I levels. The degree of suppression of IGF-I and growth hormone will be determined at two dose levels of SMS 291-955 pa LAR. Tamoxifen will be added to two of the cohorts to determine if the additive effects of tamoxifen and SMS 201-955 pa LAR will lead to additional reduction of circulating IGF-I and growth hormone levels. Arginine-stimulated GH tests to assess levels of growth hormone in the blood will be administered pre-treatment evaluation up to three times, one time on weeks 2, 8, 16, 28, 40, 52, and one month post last dose of SMS 201-955 pa LAR. The four cohorts for this study will receive 60 or 90 mg SMS 201-955 pa LAR injectable every four weeks for up to 52 weeks. Two of the cohorts will receive 10 mg Tamoxifen on a daily basis.

Although there seems to be no benefit from improving the histologic response rate or long-term survival of intra-arterial infusion of cisplatin for localized osteosarcoma of extremities with IOR/OS-3, IOR/OS-5, and COSS 86 protocols, such a treatment strategy is still believed to potentially increase the tumoricidal effect with an increase in higher local concentrations of the infused agents combined with longer tissue exposure time. Besides, the relationship of chemotherapy-induced necrosis and surgical margins is still the main concern for localized osteosarcoma patients to achieve long-term survival. The investigators intend to analyze the gain and loss from transcatheter intra-arterial limb infusion of cisplatin for extremity osteosarcoma in the past six years.

After standard multimodal therapy, the prognosis of relapsed and unresectable high-grade osteosarcoma is dismal and unchanged over the last decades. We have already finished a prospective trial about apatinib for advanced osteosarcoma(NCT02711007) and find it has a objective response rate of aproximately 45% with median progression-free survival around 5 months. Thus, the investigators explored apatinib activity together with anti-PD1 therapy in order to induce durable response in patients with relapsed and unresectable osteosarcoma after the failure of first-line or second-line chemotherapy. Apatinib is a small-molecule vascular endothelial growth factors receptor (VEGFR) tyrosine kinase inhibitor, similar to pazopanib, but with a binding affinity 10 times to VEGFR-2 comparing with pazopanib or sorafenib. SHR-1210 is a humanized anti-PD-1 monoclonal antibody.

The investigators have recently demonstrated that argininosuccinate synthase 1 (ASS1) expression is silenced in 88% of all sarcomas (n=708), and that this loss is associated with a decreased overall survival. Using the extracellular arginine depleting enzyme PEGylated arginine deiminase (ADI-PEG20), an extracellular arginine depleting enzyme, the investigators demonstrated ADI-PEG20 induces a prosurvival metabolic reprogramming in ASS1-deficient sarcomas that redirects glucose into the serine/folate pathway directing the carbons from glucose into pyrimidine biosynthesis, thus sensitizing cells to death by the pyrimidine antimetabolite gemcitabine by using metabolomics. The synthetic lethality was increased by the addition of docetaxel. Therefore a phase II clinical trial of ADI with gemcitabine and docetaxel, a standard second line therapy for soft tissue sarcoma will be conducted to determine if the clinical benefit rate of gemcitabine and docetaxel is improved by the metabolic changes induced by ADI-PEG20. Recently published data shows that priming ASS1-deficient tumors with ADI-PEG 20 and docetaxel improves the effect of gemcitabine. Therefore, a cohort of patients consisting of ten patients diagnosed with either osteosarcoma or Ewing's sarcoma (ideally five of each), and five patients diagnosed with small cell lung cancer will be included as an exploratory cohort. Enrollment to Cohort 2 will occur concurrently with Cohort 1.